Clinical translation of microbe‐based therapies: Current clinical landscape and preclinical outlook

Abstract

Next generation microbe‐based therapeutics, inspired by the success of fecal microbiota transplants, are being actively investigated in clinical trials to displace or eliminate pathogenic microbes to treat various diseases in the gastrointestinal tract, skin, and vagina. Genetically engineered microbes are also being investigated in the clinic as drug producing factories for biologic delivery, which can provide a constant local source of drugs. In either case, microbe‐therapeutics have the opportunity to address unmet clinical needs and open new areas of research by reducing clinical side effects associated with current treatment modalities or by facilitating the delivery of biologics. This review will discuss examples of past and current clinical trials that are investigating microbe‐therapeutics, both microbiome‐modulating and drug‐producing, for the treatment of a range of diseases. We then offer a perspective on how preclinical approaches, both those focused on developing advanced delivery systems and those that use in vitro microbiome model systems to inform formulation design, will lead to the realization of next‐generation microbe‐therapeutics.

A gut butyrate‑producing bacterium <em>Butyricicoccus&nbsp;pullicaecorum</em> regulates short‑chain fatty acid transporter and receptor to reduce the progression of 1,2‑dimethylhydrazine‑associated colorectal cancer

“…A greater understanding of gut microbes may lead to different use of medicine in CRC. Gut microbe-based therapeutics are actively used for cancer treatment or prevention ( 39 ). Numerous studies have reported on the use of microbial markers, including microbes and metabolites, to target CRC ( 40 , 41 ).…”

Extrinsic Factors Shaping the Skin Microbiome

“…However, only ZPT-containing lipid body wash significantly reduced Staphylococcus abundance at the genus level, and S. aureus at the species level, probably due to the deposition of this active material on skin surfaces and its subsequent interaction with bacterial cells to control their population. Nevertheless, assessment of SCORAD (SCORing of Atopic Dermatitis) scores revealed that AD severity remained unchanged in treated patients [ 68 ], supporting the theory that the impact of microbes in AD results from bacterial communities and their interactions, rather than from isolated bacteria [ 21 , 80 , 81 ].…”

Cell therapies in the clinic

“…Although metabolic disorders account for only 8% of the indications for microbes, it is worth mentioning this unique niche, as very few cell therapies are investigated for this indication. Microbes exert therapeutic mechanisms of action by (i) displacing pathogenic microbiomes to restore symbiosis and (ii) producing therapeutic biomolecules, a function enabled by genetic modification 33 …”

“…Forty‐eight microbe‐based clinical trials were identified (3% of the total trials) (Figure 2) and separated into four main categories based upon consortia‐based/single strain‐based therapy status and indication (Table 8). 4,33,101 Undefined, consortia‐based therapies consist of microbes collected from healthy patient stool banks 101 . The resulting microbe therapeutic ranges from unpurified material stripped only of harmful components (e.g., viruses, pathogens) to material stripped of several species in order to isolate specific microbial phyla with some, or all, individual species remaining unidentified.…”